Transcription
As you interact with industry and your providers to understand what are some of the nuances of clinical trials, and there's no one better to talk about it than Kim. She's a clinical research specialist. She's been in this field for over 30 years. Uh, and she works closely there with Avon Sante to really uh conduct clinical trials. And in fact, something that the AHA wants to do is to maybe think about partnering with the CRO to help and make sure that we get clinical trials done effectively and efficiently. So, Kim, thank you for joining us for the first time ever coming to the AHA.
Kim Ruella, [applause]
I got the old lady glasses on because I didn't know if I could see the back. And unlike Craig, I don't like to freewheel, right? So, um, clinical trials is not a space where we should do that. Um, but I wasn't sure I'd be able to see the screen, so I'll leave my glasses there. Um, big thank you to Megan and Dr. Dr. Lambert for having me. Um, Megan, I will trust that you'll keep me on track as I get talking about clinical trials. Um, I, it's something I'm very passionate about. As Craig mentioned, I've been in this industry for over three decades, which I realize also ages me, but hopefully gives me a little bit of experience and expertise that I can share with all of you. This is a phenomenal conference so far. I am delighted to be here. It is not typical that I get to come and talk to patients. So when Craig invited me to come and talk about clinical trials, I jumped at the chance.
The problem with these kinds of conferences is that you hear people talking throughout their um sessions and you go, "Oo, I want to touch on that. I want to tie that in." So I'm probably going to take us on a little bit of a detour, but I really do want to get to the heart of clinical trials. You've heard Dr. Weineberg and Dr. talk about research and studies, and there are so many things that happen um in the research space before a clinical trial. Um, there are academic studies, there are plant-based medicines, we're talking about stem cell research, there's a whole bunch of development and research that goes into AIH before you even get to a clinical trial. So this is years of of different ways of studying the disease. It's different ways of treating. As you heard them all say, this is an extremely heterogeneous disease, right? Each one of you presents a little bit differently. And they're all working in their own patient groups with their own patients to understand what is really happening with the disease, which then leads us to the next part, which is clinical trials.
So what are they? Um, again, they are very structured. It is a scientific study that is designed specifically to evaluate very specific endpoints that will help us look at new potential treatments. Those treatments could be um new drugs. They could be combinations of drugs. They could be diagnostic tools. They could be devices. All of this is going to eventually help with the treatment of AIH or any other disease. So I'm taking this really back to the basics. We're talking about clinical trials in general. So there's a lot of this that will be really relevant for all of you, but this is the basics of clinical trials across disease types, across indications, across populations. The main goal of clinical trials is to make sure that any new treatment, whether it be a drug, a combination of drugs, is safe and effective. There are lots of things that we can take that may be safe. And the effectiveness, is it really any different than not doing anything? So, the main goal of clinical trials is safety and effectiveness. We want to look at that before these drugs are made available to the public or larger populations of patients.
There are regulations and regulations and regulations. They must be followed in order for clinical trials to even happen. There are a ton of people that are looking at this study. Some of them are here today. You're going to hear about some results from some early phase um projects that have concluded in AIH specifically. All of those studies are regulated by not only um the FDA in the US but also ethics committees. So there are separate committees that are not tied to the research that will look at the study design and say, "Is this design safe for patients? Are we going to get valuable results at the end of the day?" The results might not be favorable, right? The study may fail, but at the end of the day, can we feel comfortable with patients taking these drugs, participating in the study? First and foremost, there's regulations. Patient safety and well-being are always going to be at the forefront of your clinical team that is driving the study. So, they are always going to check in on safety. They're always going to make sure that you are tolerating the medication well.
Clinical trials are voluntary. They're completely voluntary. You should feel no pressure from a physician or anyone else to participate in a clinical trial. As a patient, it is your right to decline participation, but I would encourage you to learn as much as you can about any clinical trials that might be offered. Again, rare disease, unique situation. There is no treatment out there for AIH, right? So, if you're being offered participation in a clinical trial, it is completely voluntary. You have every right in the world to ask a million questions about the study. And we're going to go through what some of those good questions might be, but you should not feel pressure in any way to actively participate in a clinical trial.
Before a clinical trial starts, let's say you're presented one. You think, "Oh, this is a great idea. My doctor thinks it's the right fit for me. I like the nursing team. I trust them. They all think this is a good idea." Before you do anything, you are going to be asked to provide informed consent. And I want to highlight this because it's probably one of the most important pieces of a clinical trial. It's not just a form that you're going to sign to say like, "Yes, I agree to my fibro scan." I know it's a document. It's a process. The informed consent will take you through all the risks and benefits of participating in that study. It will take you through, "Am I going to get the drug? Am I going to get a controlled placebo? Um, what are the risks? What do they know about the safety of this drug? Um, what are the potential benefits?" Um, all of that is going to be listed out for you before you actively agree to participate in the trial. I like to highlight that because it's something that often gets missed and it's something that you should be considering throughout the course of the study. Again, participation is voluntary. You have the opportunity to drop out at any time if you don't like whatever. You don't, you're not tied to the course of the study.
What I will say from somebody who does this for a living is that it is really important that you, as the patient, understand the commitment that you're making. Okay. So, we're going to go through in a couple slides. I'm going to take you through some good questions that you want to ask before you agree to participate in the study because getting the patients into the study is one thing, but seeing them through the entire course of this study is something else entirely. People drop out for a number of reasons, but you should make sure that you understand upfront what is going to be asked of you as you participate in the trial.
Okay, why are they important? Um, they are critical for ensuring the safety and efficacy of the drugs, right? Again, before they get to large populations of patients, um, they contribute significantly to the understanding um of different health conditions, right? So clinical trials in AIH, they're not only going to help the companies understanding the drugs or trying to develop the drugs, but they're going to help your providers understand AIH just a little bit better. That's going to help with further developments down the road. It's going to help with patient care. It's going to help with all of the patients that are also not participating in the clinical trial. It gives them just more information to work with, which is which is extremely um essential when we're talking about the rare diseases. The more we can study them, the more development we can have on the back end.
I'm not going to read through all of these because I think Megan's going to try and keep me on time, but I know the slides will be available for everyone. Um, uh, providing access to therapies that are not yet available is also a key point. um, getting more attention, more um focused time with primary caregivers that are really experienced in this research field. All of those um ultimately will benefit the patients um and understanding the disease just a little bit better. [snorts]
Who participates in clinical trials? Um, there's a number, there's a variety of reasons that people do actively participate in trials. Um, you'll hear me talk in a minute about early phase studies. Um, primarily those are done in healthy volunteers. Um, and you're thinking to yourself, why would somebody do that, right? These are people that are committed to kind of helping others um, advancing research um, giving a better kind of baseline for patients that might be more um in need than they are. So that's a big driving force in a lot of the healthy volunteer studies. Um, people with an illness or an underlying disease also part um, participate to help other patients. Um, patients impacted by the disease also might um, get additional care, additional attention, like I said, from caregivers. Um, they offer a lot of hope and opportunity to people um, in helping those research again um, plan for the future and have better instruments to measure these diseases as we move forward.
Okay, so now you've been approached about a clinical trial. You're thinking about giving your informed consent. You haven't done that yet. What do you need to know as a patient um before you make this commitment? Right? So, a lot of this information is going to be listed out in that informed consent document that we talked about. But these are conversations. These are questions that you should make sure you understand the answer to before you commit. Why is the study being done? Um, how long is the study? How long am I going to be involved in this? Some can be very short. Others might be a lot longer. So make sure you understand what the time commitment is. Um, if I'm going to be given the treatment or a placebo or a control, how am I going to be given it? Is it an IV? Is it a pill? Um, do I have to come to the office every time to take it? Is it something you're going to send home with me and I can take it at home? Um, how many visits do I need to make? Where are the visits going to be? Is it somewhere that is local to me? Do I need to arrange for transportation? Um, all of these things are things you should definitely understand before you agree to participate. Um, do you have to pay for any part of the study? Is insurance going to cover any part of this? In some of the rare diseases, right, these are are not well known, there's not a lot of diagnostics. Many of the costs will be prov, will be covered by the study itself. But if there are standard of care labs that are getting drawn, standard of care fiber scans, get whatever it is, you want to make sure that you understand what your financial commitment or what your insurance may or may not cover for this. Um, what are the risks of this study? Um, how might this benefit me? Again, there's a whole host of questions that you need to make sure you're comfortable with. And again, your healthcare provider, the people running the trial, they will be able to answer all of this upfront. They know the answers. They, they have probably asked all of these questions um themselves, so they, they can readily help guide you and provide this information for you.
Megan's given me the the s, the sign. So I'm going to talk a little quickly. I am just going to take us through the different phases of clinical trials. As I said before, there's a lot of research that happens before we even get to the clinical trial phase. Um, but primarily once we get to that point where we have a medication or a treatment or a combination of treatments, there's four different phases of the studies. Phase 1 through 4. One is the earliest phase, first in humans. This is primarily focused on safety. Small groups of patients um, typically healthy volunteers, but sometimes they can be in patients depending on the disease under study. There is a strict, strict monitoring of very gradual dosing. Any events that are experienced throughout any of the phases are reported. You heard a lot of conversation about, you know, what are you taking, how are you feeling, any changes throughout the course of a clinical trial, you should always report that to your provider. But any events that are um, experienced, no matter how small they are, um, you definitely should report. Over 70% of drugs in phase one can be eligible to move on to phase two. That seems really high to me, but those are the current numbers. And I think it's because there's so much research happening right now. There's a lot more molecules um, in in um, development.
I'm going to talk quickly through phases two through four. Phase two starts to look at safety and effectiveness. Um, it is really looking at the optimiz, at the optimal dose that should be used in large-scale populations. It is a balance of safety and benefit with safety always being at the forefront. These can be up to somewhere between 100 and 300 patients. So a little bit a larger group sample size. Typically they use a control to um, reduce the bias. Right? So you might get a placebo or some other standard of care as a comparator. They help to identify the key endpoints that are going to be used for later larger studies. And so these are really important. You might think the fiber scan is the best thing, but then during a phase two they realize, oo, you know what? We need to do the liver biopsy. That's really the best way to get an endpoint. I'm just throwing those out for examples. Practitioners, don't don't yell at me there. But just different ways of finding the best clinical endpoints as we go into larger studies. Roughly a third of the compounds that are into phase two will go into phase three. So you see a significant drop off from phase one to phase two.
Phase three studies. Now we have a treatment that is showing really promising results. I think you're going to hear about a compound later. Um, some results that are leading into a phase three study, which is really exciting. Um, safety and efficacy across a large and diverse population of patients. Okay. So, um, it's not just, you know, 100 women aged 50 to 65. This is a much more diverse population that they're going to try and study this treatment across. Um, they are going to evaluate efficacy as well as monitoring safety. Patient numbers can go up to the thousands and they are strictly designed to further reduce bias. So you'll see as you go through phase one, phase two, phase three, everything gets a little tighter and a little tighter and a little tighter, little less freewheeling, right? There's a lot more regulations about what this study is going to look like. Um, if a phase three study is successful, typically that company will then submit that as a new drug application to an agency for review and potentially subsequent approval.
Phase four, I'm out of time, so I'm not gonna touch on one second. Um, postmarketing surveillance. These typically are studies that are done after the drug has been approved. So, what else do we need to know that's happening in the real world with patients that are actually taking this drug? What other kind of information can we study to further develop the compound? um, or maybe that compound was less than ideal, but we can moderate it a little bit in the lab and make it just a little bit more effective um, and a little bit more useful for the patient population.
I think that's all for me. Um, I do want to just stress that clinical trials are a vital component of medical research. Um, they don't only kind of advance healthcare, but they do really improve the quality of life for patients. Um, I am happy to answer any questions. I know we've got a little Q&A. Again, I am not a clinician. I'm not out there treating patients. Um, but I do have a lot of experience in developing, designing, and executing clinical trials. I'm happy to answer questions as part of the panel and then I'll be here today and tomorrow. So, if anybody has questions after that, I'm I'm also here.
>> Great. Thank you, G.
>> Yeah, sure. Sorry, I'm over.